Treatment of Euglycemic DKA Associated with SGLT2 Inhibitors (Sotagliflozin and Empagliflozin)
Euglycemic diabetic ketoacidosis (eDKA) associated with SGLT2 inhibitors should be treated with standard DKA protocol including intravenous insulin infusion with concurrent dextrose administration to maintain euglycemia, aggressive fluid resuscitation, and electrolyte replacement. 1
Immediate Management
Recognition and Diagnosis
- Look for metabolic acidosis with elevated anion gap despite normal or only mildly elevated blood glucose levels (<180-200 mg/dL)
- Check for elevated serum ketones and positive urine ketones
- Assess for precipitating factors: surgery, acute illness, reduced carbohydrate intake, alcohol use, or medication non-compliance 2, 3
Initial Treatment
Fluid Resuscitation
- Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hr for the first hour
- Continue IV fluids at 250-500 mL/hr based on hemodynamic status and hydration needs
Insulin Therapy
- Start IV regular insulin at 0.1 units/kg/hr
- Critical difference from standard DKA: Add dextrose infusion (D5W or D10W) concurrently to maintain blood glucose 150-200 mg/dL 4
- Continue insulin infusion until ketoacidosis resolves (anion gap normalizes)
Electrolyte Replacement
- Monitor and replace potassium, maintaining levels >4.0 mEq/L
- Monitor phosphate and magnesium levels and replace as needed
- Bicarbonate therapy is generally not recommended unless pH <6.9 1
Monitoring
- Check blood glucose hourly
- Monitor electrolytes, blood gases, and ketones every 2-4 hours
- Assess fluid status and urine output regularly
Ongoing Management
Transition to Subcutaneous Insulin
- Once ketoacidosis resolves (anion gap normalizes, pH >7.3), transition to subcutaneous insulin
- Administer subcutaneous insulin 2-4 hours before stopping IV insulin infusion to prevent recurrence of ketoacidosis 1
- Initial subcutaneous insulin regimen should include both basal and bolus components
SGLT2 Inhibitor Management
- Permanently discontinue the SGLT2 inhibitor (sotagliflozin or empagliflozin) 2
- Consider alternative diabetes medications based on patient characteristics
- If SGLT2 inhibitor is needed for heart failure or CKD benefits, careful risk-benefit assessment should be performed by specialists
Prevention of Recurrence
Patient Education
- Educate patients on recognizing early symptoms of eDKA: nausea, vomiting, abdominal pain, fatigue, and dyspnea
- Implement "sick day" protocols: hold SGLT2 inhibitors during acute illness, reduced food intake, or planned surgical procedures 5
Perioperative Considerations
- Discontinue SGLT2 inhibitors at least 3-4 days before elective surgery 1
- Note that eDKA can occur even when SGLT2 inhibitors are discontinued 48 hours before surgery 6
- Resume SGLT2 inhibitors only after full recovery from surgery and normal oral intake is established
Special Considerations
Risk Factors for eDKA
- Reduced insulin doses or insulin omission
- Major surgery or acute illness
- Reduced caloric or carbohydrate intake
- Alcohol consumption
- Pancreatic insulin deficiency (LADA, type 1 diabetes, pancreatitis) 7
Diagnostic Challenges
- Normal or minimally elevated blood glucose levels often delay diagnosis
- High index of suspicion needed in patients on SGLT2 inhibitors presenting with symptoms of DKA despite near-normal glucose levels 3
- Always check ketones and blood gases in symptomatic patients on SGLT2 inhibitors regardless of glucose levels
Follow-up Care
- Reassess diabetes management plan after resolution of eDKA
- Consider endocrinology consultation for medication adjustment
- Ensure close monitoring during the first few weeks after discharge
- Provide clear written instructions about avoiding SGLT2 inhibitors in the future
By following this comprehensive approach to managing euglycemic DKA associated with SGLT2 inhibitors, clinicians can effectively treat this potentially life-threatening condition while minimizing complications and preventing recurrence.